Topical and transdermal drug delivery provide many advantages over other common delivery routes like oral, subcutaneous, and intravenous. These advantages include avoidance of major degradative pathways associated with the GI tract, reduction in side effects associated with systemic toxicity, and needle-free drug administration. Brown, et al., “Dermal and transdermal drug delivery systems: current and future prospects”, Drug Delivery, 13:175-87 (2006). Unfortunately, the outermost layer of the skin, the stratum corneum (SC), functions as a barrier to most foreign material and severely limits passive diffusion of many molecules. To overcome this barrier, several strategies have been employed including the use of chemical penetration enhancers (CPEs). CPEs have been shown to enhance transport through the skin, for a variety of molecules, by disrupting the lipid composition and organization in the SC. Karande, et al., “Design principles of chemical penetration enhancers for transdermal drug delivery”, Proceedings of the National Academy of Sciences of the United States of America, 102:4688-93 (2005). However, the extent of lipid disruption often correlates closely with skin irritation. Karande 2005. Therefore, a balance between transport enhancement and skin irritation is often required before a CPE-based drug formulation can be commercialized.
Concurrently, for the treatment of bacterial skin infections, a second transport barrier to drug delivery exists—the bacterial biofilm. Biofilm-protected bacteria account for 65% of bacterial infections in humans and are 50-500 times more resistant to antibiotics than unprotected bacteria. Palmer, et al., “Molecular techniques to detect biofilm bacteria in long bone nonunion: a case report”, Clinical orthopaedics and related research, 469:3037-42 (2011). The antibiotic resistance is due to the transport barrier posed by extracellular polymeric substances (EPS), e.g. polysaccharides, humic acids and nucleic acids. Although the chemical composition of the SC and bacterial biofilm are distinctive, overcoming the transport barrier posed by the SC and biofilm can be accomplished in a similar manner, such as through fluidization or extraction of the barrier components by a suitable solvent.
There is a need for compositions and methods that improve transdermal transport, but do not irritate the skin. There is also a need for improved compositions to inhibit microbial growth on biological and synthetic surfaces.
Therefore it is an object of the invention to provide compositions for improving transdermal transport of therapeutic, prophylactic, or diagnostic agents.
It is a further object of the invention to provide improved compositions for the treatment of diseases and disorders within the skin, such as infections.
It is a further object of the invention to provide methods and compositions for inhibiting microbial growth.
It is yet a further object of the invention to provide methods for improving transdermal transport of therapeutic, prophylactic, or diagnostic agents.
It is a still further object of the invention to provide improved methods for treatment of diseases and disorders of the skin.